Public Acceptance of Measures to Control Infectious Diseases Under Different Scenarios of Severity and Transmissibility.

OBJECTIVES: Public health measures to control future epidemic threats of contagious disease, such as new variants of COVID-19, may be usefully informed by evidence about how acceptable they are likely to be, and the circumstances that condition this acceptance. This study considers how the acceptability of nonpharmaceutical interventions (NPIs) might depend on scenarios about the severity and transmissibility of the disease. METHODS: A telephone survey was conducted among a representative cross-sectional sample of the Spanish adult population. Each respondent was randomly assigned to 1 of 4 possible hypothetical scenarios about the severity and transmissibility of the disease. Participants' responses about the acceptability of 11 NPI under this scenario were analyzed using multivariate regression and latent class cluster analysis. RESULTS: A high risk of severe disease increases the acceptability of mask wearing, social distancing outdoors, lockdown, and isolation of infected cases, close contacts, and the vulnerable. A scenario in which the disease is highly transmissible would increase the acceptability of NPI that restrict movement and isolation. Most respondents would broadly accept most NPI in situations when either the severity or transmissibility was high. CONCLUSIONS: This study showed that people are more willing to accept NPIs such as mask wearing, social distancing outdoors, lockdown, and isolation in severe disease scenarios. A highly transmissible disease scenario increases the acceptability of NPIs that isolate. A majority would broadly accept NPIs to counter public health emergencies, whereas 3% to 9% of the population would always be strongly against.

INES: Interactive tool for construction and extrapolation of partitioned survival models.

BACKGROUND: INES (INteractive model for Extrapolation of Survival and cost) provides an open-access tool powered by R that implements three-state partitioned survival models (PSM). This article describes the properties of the tool, and the situations where INES may or may not be suitable. METHODS: INES is designed to be used by investigators or healthcare professionals who have a good grasp of the principles of economic evaluation and understand the strengths and weaknesses of partitioned survival models, but are not sufficiently familiar with a statistical package such as Excel or R to be able to construct and test a de-novo PSM themselves. INES is delivered to the user via a batch file. Once downloaded to the user's hard drive, it interacts with the user via a portable version of R with web interactivity built in Shiny. INES requires absolutely no knowledge of R and the user does not need to have R or any of its dependences installed. Hence the user will deal with a standalone Shiny app. Inputs (digitalized survival curves, unit costs, posology, hazard ratios, discount rate) can be uploaded from a template spreadsheet. RESULTS: The INES application provides a seamlessly integrated package for estimating a set of parametric hazard functions for progression free and overall survival, selecting an appropriate function from this menu, and applying this as an input to a PSM to calculate mean costs and quality-adjusted life years. Examples are given that may serve as a tutorial. CONCLUSION: INES offers a rapid, flexible, robust and transparent tool for parametric survival analysis and calculating a PSM that can be used in many different contexts.

Safety and immunogenicity of the protein-based PHH-1V compared to BNT162b2 as a heterologous SARS-CoV-2 booster vaccine in adults vaccinated against COVID-19: a multicentre, randomised, double-blind, non-inferiority phase IIb trial.

Background: A SARS-CoV-2 protein-based heterodimer vaccine, PHH-1V, has been shown to be safe and well-tolerated in healthy young adults in a first-in-human, Phase I/IIa study dose-escalation trial. Here, we report the interim results of the Phase IIb HH-2, where the immunogenicity and safety of a heterologous booster with PHH-1V is assessed versus a homologous booster with BNT162b2 at 14, 28 and 98 days after vaccine administration. Methods: The HH-2 study is an ongoing multicentre, randomised, active-controlled, double-blind, non-inferiority Phase IIb trial, where participants 18 years or older who had received two doses of BNT162b2 were randomly assigned in a 2:1 ratio to receive a booster dose of vaccine-either heterologous (PHH-1V group) or homologous (BNT162b2 group)-in 10 centres in Spain. Eligible subjects were allocated to treatment stratified by age group (18-64 versus ≥65 years) with approximately 10% of the sample enrolled in the older age group. The primary endpoints were humoral immunogenicity measured by changes in levels of neutralizing antibodies (PBNA) against the ancestral Wuhan-Hu-1 strain after the PHH-1V or the BNT162b2 boost, and the safety and tolerability of PHH-1V as a boost. The secondary endpoints were to compare changes in levels of neutralizing antibodies against different variants of SARS-CoV-2 and the T-cell responses towards the SARS-CoV-2 spike glycoprotein peptides. The exploratory endpoint was to assess the number of subjects with SARS-CoV-2 infections ≥14 days after PHH-1V booster. This study is ongoing and is registered with ClinicalTrials.gov, NCT05142553. Findings: From 15 November 2021, 782 adults were randomly assigned to PHH-1V (n = 522) or BNT162b2 (n = 260) boost vaccine groups. The geometric mean titre (GMT) ratio of neutralizing antibodies on days 14, 28 and 98, shown as BNT162b2 active control versus PHH-1V, was, respectively, 1.68 (p < 0.0001), 1.31 (p = 0.0007) and 0.86 (p = 0.40) for the ancestral Wuhan-Hu-1 strain; 0.62 (p < 0.0001), 0.65 (p < 0.0001) and 0.56 (p = 0.003) for the Beta variant; 1.01 (p = 0.92), 0.88 (p = 0.11) and 0.52 (p = 0.0003) for the Delta variant; and 0.59 (p ≤ 0.0001), 0.66 (p < 0.0001) and 0.57 (p = 0.0028) for the Omicron BA.1 variant. Additionally, PHH-1V as a booster dose induced a significant increase of CD4+ and CD8+ T-cells expressing IFN-γ on day 14. There were 458 participants who experienced at least one adverse event (89.3%) in the PHH-1V and 238 (94.4%) in the BNT162b2 group. The most frequent adverse events were injection site pain (79.7% and 89.3%), fatigue (27.5% and 42.1%) and headache (31.2 and 40.1%) for the PHH-1V and the BNT162b2 groups, respectively. A total of 52 COVID-19 cases occurred from day 14 post-vaccination (10.14%) for the PHH-1V group and 30 (11.90%) for the BNT162b2 group (p = 0.45), and none of the subjects developed severe COVID-19. Interpretation: Our interim results from the Phase IIb HH-2 trial show that PHH-1V as a heterologous booster vaccine, when compared to BNT162b2, although it does not reach a non-inferior neutralizing antibody response against the Wuhan-Hu-1 strain at days 14 and 28 after vaccination, it does so at day 98. PHH-1V as a heterologous booster elicits a superior neutralizing antibody response against the previous circulating Beta and the currently circulating Omicron BA.1 SARS-CoV-2 variants in all time points assessed, and for the Delta variant on day 98 as well. Moreover, the PHH-1V boost also induces a strong and balanced T-cell response. Concerning the safety profile, subjects in the PHH-1V group report significantly fewer adverse events than those in the BNT162b2 group, most of mild intensity, and both vaccine groups present comparable COVID-19 breakthrough cases, none of them severe. Funding: HIPRA SCIENTIFIC, S.L.U.

Cost-effectiveness of carotid endarterectomy in symptomatic patients.

BACKGROUND: Medical therapy for stroke prevention has improved significantly over the past 30 years. Recent analyses of medically treated cohorts have suggested that early rates of stroke may have reduced, and reports of the safety of carotid surgery have also shown improvements. Since the effectiveness of carotid surgery versus medical therapy was established in the 1990s, there is an urgent need to evaluate whether surgery remains cost-effective in the UK. METHODS: A decision model was developed to estimate the lifetime costs and utilities of modern medical therapy with and without carotid endarterectomy in patients with symptomatic stenosis from the perspective of the UK National Health Service. The base-case population consisted of adults aged 70 years with 70-99 per cent stenosis. Model data were obtained from clinical studies and wider literature. Univariate and probabilistic sensitivity analyses were carried out. RESULTS: In the base-case scenario, the 5-year absolute risk reduction with carotid endarterectomy was 5 per cent, and the incremental cost-effectiveness ratio was €12 021 (exchange rate £1 GBP = €1.1125 (Tuesday 1 January 2019)) per quality-adjusted life-year. Surgery was more cost-effective if performed rapidly after presentation. In patients with 50-69 per cent carotid stenosis, surgery appeared less clinically effective. However, there was considerable uncertainty. CONCLUSION: Surgery may not now be clinically effective and cost-effective in those with moderate carotid stenosis. However, these results are uncertain because of the limited data on modern medical therapy and an RCT may be justified.

Challenges for Economic Evaluations of Advanced Therapy Medicinal Products: A Systematic Review.

OBJECTIVES: Advanced therapy medicinal products (ATMPs) are drugs for human use for the treatment of chronic, degenerative, or life-threatening diseases that are based on genes, tissues, or cells. This article aimed to identify and critically review published economic analyses of ATMPs. METHODS: A systematic review of economic analyses of ATMPs was undertaken. Study characteristics, design, sources of data, resources and unit costs, modeling and extrapolation methods, study results, and sensitivity analyses were assessed. RESULTS: A total of 46 economic analyses of ATMP (from 45 articles) were included; 4 were cell therapy medicinal products, 33 gene therapy medicinal products, and 9 tissue-engineered products. 30 therapies had commercial marketing approval; 39 studies were cost-utility analysis, 5 were cost-effectiveness analysis, and 2 were cost only studies. Four studies predicted that the ATMP offered a step change in the management of the condition and 10 studies estimated that the ATMP would offer a lower mean cost. CONCLUSIONS: Comparison with historical controls, pooling of data, and use of techniques such as mixture cure fraction models should be used cautiously. Sensitivity analyses should be used across a plausible range of prices. Clinical studies need to be designed to align with health technology assessment requirements, including generic quality of life, and payers should aim for clarity of criteria. Regulators and national payers should aim for compatibility of registers to allow interchange of data. Given the increasing reliance on industry-funded economic analyses, careful critical review is recommended.

Consumers' Preferences and Willingness to Pay for Personalised Nutrition.

INTRODUCTION: Personalised nutrition (PN) has great potential for disease prevention, particularly if coupled with the power and accessibility of mobile technology. However, success of PN interventions will depend on the willingness of users to subscribe. This study investigates the factors associated with potential users' perceived value of PN and heterogeneity in these values. METHODS: A discrete choice experiment was carried out in a representative sample (N = 429 valid responses) from the adult population in Spain. The results were analysed in line with McFadden's Random Utility Theory, using conditional and mixed logit models in addition to a latent class logit model. RESULTS: The conditional and mixed logit models revealed the existence of a significant preference and willingness to pay for personalised nutrition, but the effect on average was not large for the highest level of personalisation. The latent class logit revealed four classes of respondent: those who would be likely to pay for a high level of personalised nutrition service, those who would use it if it were heavily subsidised, those who would use only a basic nutrition service, and those who would not be willing to engage. These results could be useful for the design and targeting of effective personalised nutrition services. CONCLUSIONS: Over half of adults currently perceive some individual benefit in a high level of PN, which may justify some degree of public subsidy in investment and delivery of such a service.

A Predictive Model and Risk Factors for Case Fatality of COVID-19.

This study aimed to create an individualized analysis model of the risk of intensive care unit (ICU) admission or death for coronavirus disease 2019 (COVID-19) patients as a tool for the rapid clinical management of hospitalized patients in order to achieve a resilience of medical resources. This is an observational, analytical, retrospective cohort study with longitudinal follow-up. Data were collected from the medical records of 3489 patients diagnosed with COVID-19 using RT-qPCR in the period of highest community transmission recorded in Europe to date: February-June 2020. The study was carried out in in two health areas of hospital care in the Madrid region: the central area of the Madrid capital (Hospitales de Madrid del Grupo HM Hospitales (CH-HM), n = 1931) and the metropolitan area of Madrid (Hospital Universitario Príncipe de Asturias (MH-HUPA) n = 1558). By using a regression model, we observed how the different patient variables had unequal importance. Among all the analyzed variables, basal oxygen saturation was found to have the highest relative importance with a value of 20.3%, followed by age (17.7%), lymphocyte/leukocyte ratio (14.4%), CRP value (12.5%), comorbidities (12.5%), and leukocyte count (8.9%). Three levels of risk of ICU/death were established: low-risk level (<5%), medium-risk level (5-20%), and high-risk level (>20%). At the high-risk level, 13% needed ICU admission, 29% died, and 37% had an ICU-death outcome. This predictive model allowed us to individualize the risk for worse outcome for hospitalized patients affected by COVID-19.

Monitorización de la eficacia de la descontaminación microbiana de superficies / No disponible

No disponible